Non-infectious Interstitial Lung Disease
Bahman Saatian, M.D.
Pulmonary Critical Care Medicine
UC Irvine Medical Center
September 8 2014
OBJECTIVES
• Review the spectrum of ILD
• Identify the clues on presentation to make the diagnosis
• Review the common radiographic findings in ILD
• Role of BAL, TBBX and OLB in diagnosis of ILD
• An algorithm to make the diagnosis
ILDs are heterogeneous group of disorders
that are classified together because of similar
clinical, physiologic radiographic, or pathologic
manifestation.
Pulmonary Interstitium
• Alveolar lining cells (types 1 and 2)
• Thin elastin-rich connective component containing
capillary blood vessels.
What is Pulmonary Interstitium?
• Between the epithelial and
endothelial basement membrane
• Expansion of the interstitium
compartment by inflammation
with or without fibrosis
- Necrosis
- Hyperplasia
- Collapse of basement membrane
- Inflammatory cells
• Interstitial reflects the pathological abnormality begins
in the interstitium → extensive alteration of alveolar and
airway architecture.
Pathogenesis
• The pathogenesis of ILD is unknown.
• Studies have shown that immune cells and their cytokines
play an important role in the course of ILD.
Pathogenesis
• The pathogenesis of ILD is unknown.
• Studies have shown that immune cells and their cytokines
play an important role in the course of ILD.
• Intra-alveolar inflammation.
• Immune cells and their cytokines injure epithelial and
endothelial cells.
• Intra-alveolar fibrosis / collapse
Classification
Classification
• Associated with known causes
• Idiopathic
Treatment choices and prognosis vary among different
types of ILDs.
Coultas, et al. AJRCCM, 1994, 150, 679-72.
Classification of idiopathic Interstitial Pneumonia
An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial
Pneumonias, 2013
Clinical Assessment
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History
Physical Exam
Chest Radiograph
Pulmonary Function Testing
Laboratory Studies
Tissue Examination
Clinical Manifestation
• Progressive dyspnea
• Dry cough
• Other symptoms such as fatigue, weight loss, dry mouth,
rash, joint pain, etc.
HISTORY
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Age and gender
Onset of symptoms
Past medical history
Smoking history
Family history
Prior medication use and irradiation
Occupational and environmental exposures
• Age:
Some of the ILDs are more common in certain age
groups:
Age 20-40 years
> 50years
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Sarcoidosis
CTD
LAM
EG
Idiopathic pulmonary fibrosis
• Gender
- Premenopausal female:
LAM (lymphangioleiomatosis)
- Female predominant:
ILD associated with CTD.
- Male predominant:
ILD associated with RA
Pneumoconiosis
Duration of Illness
• Acute (days to weeks)
- Acute idiopathic interstitial pneumonia (AIP)
- Eosinophilic pneumonia
- Hypersensitivity pneumonitis
- BOOP, Drug, CVD
• Subacute (weeks to months)
- Sarcoidosis
- Some drug-induced ILDs
- Alveolar hemorrhage syndromes
- COP, HSP, Cellular NSIP
- Connective tissue disease (systemic lupus erythematosus or
polymyositis)
• Chronic (months to years)
- IPF/UIP, Fibrotic NSIP, Pneumoconiosis, chronic HSP, CVD,
- Sarcoidosis
- smoking related-ILD (PLCH, RB-ILD)
SMOKING
- Histiocytosis X
- DIP
- RB-ILD
Diseases less likely to be seen in smoker:
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Hypersensditivity pneumonitis
Sarcoidosis
• In Good pasture's syndrome: 100% of smokers vs. 20%
of nonsmokers experience pulmonary hemorrhage.
• Smoking increases the risk of asbestosis in individuals
with history of asbestos exposure.
Drug-Induced Interstitial Lung Disease
Antibiotics
Nitrofurantoin, acute and chronic
Sulfasalazine
Anti-inflammatory agents
Aspirin
Gold
Pencillamine
Chemotherapeutic agents
Antibiotics
Bleomycin sulfate
Mitomycin C
Alkylating agents
Busulfan
Cyclophosphamide
Chlorambucil
Melphalan
Antimetabolites
Azathioprine
Cytosine arabinoside
Methotrexate
Miscellaneous
O2
Drugs inducing pulmonary infiltrates
and eosinophilia
Radiation
L-tryptophan
Drug-induced systemic lupus
erythematosus
Procainamide hydrochloride
Isoniazid
Hydralazine hydrochloride
The hydantoins
Pencillamine
Illicit drugs
Heroin
Methadone hydrochloride
Propoxyphene hydrochloride (Darvon)
Talc
PHYSICAL EXAMINATION
• Lung examination
• Cardiac examination
• Clubbing
• Extra pulmonary findings of systemic disease
• Bilateral basilar inspiratory crackles
• Wheezing, rhonchi, coarse crackles
• With advanced disease tachypnea, tachycardia
• At last, pulmonary hypertension and cor pulmonale
PHYSICAL FINDING
LABORATORY TESTS
LABORATORY TESTS
Anti-JO-1 Ab even in the absence of clinical
myositis, as ILD precedes the onset of myositis in
about 70% of patients with the anti-synthetase
syndrome.
SERUM MARKERS
• Surfactant protein A and B (SP-A, SP-B)
• Monocyte chemoattractant protein-1 (MCP1)
• Kerbs Von Lungren (KL)-6 a circulating, HMW glycoprotein
expressed by type II pneumocytes
SERUM MARKERS
EVALUATION
• Radiographic
- CXR
- HRCT
• Physiologic test
- PFT
- Exercise test
• Lung sampling
- BAL
- Lung biopsy
CHEST RADIOGRAPHY
• Important for diagnosis ILDs.
• Correlation between imaging and the stage of disease
(clinical or pathologic) is generally poor.
• Honeycombing (small cystic spaces) portends a poor prognosis.
• Review all previous imaging studies.
Patterns of Interstitial Lung Disease
CHEST RADIOGRAPHY
• In early stage: a diffuse ground glass pattern
• Progress: nodular, reticular or a combination
• Late stage: fibrosis, honeycomb changes
HRCT
• Both supine and prone images to recognize dependent
atelectasis and with interstitial opacities.
• Provides greater diagnostic accuracy
• Narrows the differential diagnosis
• B/l symmetric hilar adenopathy/upper lung zone reticular
opacities
- Sarcoidosis
- Granulomatous disease
• Pleural plaques with linear calcification
- Asbestosis
• Centrilobular nodules sparing subpleural region
- HP
- Sarcoidosis
- PLCH
- RB-ILD
- Follicular, and cellular bronchiolitis
• Irregular cysts with nodules in upper and middle lung
zones
- PLCH
• Subpleural / bibasilar reticular opacities, honeycomb
changes / traction bronchiectasis
- IPF
- chronic HP
- RA associated-ILD
• Diffuse, calcified, nodular, interstitial opacities in
asymptomatic patient
- VZV pneumonia
Nodular
Reticular
GROUND GLASS PATTERN
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FLUID
DAH
HP
PCP
DIP
NSIP
PAP
FDG-PET scanning
• Value in diagnosis of ILD unclear
• Lymphangitic carcinomatosis
• Sarcoidosis
• PLCH
PULMONARY FUNCTION TESTING
• Resting and exercise pulse oximetry
• Assessing the severity of lung involvement
• Obstructive, restrictive, or mixed pattern
Interstitial pattern on chest radiograph
accompanied by OBSTRUCTION
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Sarcoidosis
Lymphangioleiomyomatosis
Hypersensitivity pneumonitis
Pulmonary Langerhans cell histiocytosis
Tuberous sclerosis and pulmonary LAM
Combined COPD and ILD
Constrictive bronchiolitis
Moderate to severe reduction of DLCO in the
presence of normal lung volumes
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Combined emphysema and ILD
Combined ILD and pulmonary vascular disease
PLCH
Pulmonary LAM
REDUCED DLCO
Patients with ILD
- hypoxemic vasoconstriction
- thromboembolic disease complicating ILD with both
ILD and pulmonary hypertension (scleroderma)
CARDIOPULMONARY EXERCISE TEST
Not necessary for every patient with ILD
6 MINUTE WALK TEST
To follow ILD activity and responsiveness to treatment
especially in idiopathic pulmonary fibrosis
Pulse oximetry desaturation to ≤88% during 6MWT is
associated with a median survival of 3.21 years compared
with a median survival of 6.63 years in those who did not
desaturate below 89%
An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of
the Idiopathic Interstitial Pneumonias, 2013
BRONCHOALVEOLAR LAVAGE
• Rule out infection, DAH, PAP
LUNG BIOPSY
• TBBX
• VATS
Thank you